Abstract：
BACKGROUND: MRG002 is a novel HER2-targeted antibody-drug conjugate being investigated in the MRG002-006 trial to evaluate the efficacy and safety in HER2-positive urothelial carcinoma patients.
METHODS: This is an open-label, single-arm, multicenter phase II study. Eligibility criteria included: histologically confirmed HER2 IHC 2 + or 3 + UC, prior received ≥ 1 standard treatment. Patients in this study received MRG002 every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST 1.1.
RESULTS: As of February 24, 2023, a total of 43 patients were enrolled. The median age was 60. 9 patients were dosed at 2.6 mg/kg and 34 patients were dosed at 2.2 mg/kg. At baseline, most patients (29/43) received ≥ 2 lines of treatment and 35 (81.4%) patients had prior ICI therapy. FISH test was performed in 41 patients and 9 (22.0%) were positive. By the cut-off date, 41 patients were evaluable and the ORR was 53% (95%CI：38.9%-67.5%), with 6.9% CR, and the DCR was 83.7% (95%CI：70.0%-91.9%). The median PFS and OS for the 43 patients were 7.0 months (95%CI：5.4-NE) and 14.9 months (95%CI：11.9-NE), respectively. The ORR was 77.8% in 9 patients with positive HER2 FISH results. Most common treatment-related AEs were anemia (51.2%), alopecia (44.2%) and neutropenia (39.5%); most were grade 1 or 2.
CONCLUSIONS: Preliminary results of MRG002 demonstrated a clinically meaningful response in pretreated HER-2 positive unresectable locally advanced or metastatic UC patients. MRG002 at 2.2 mg/kg was well tolerated with a manageable toxicity.
METHODS: This is an open-label, single-arm, multicenter phase II study. Eligibility criteria included: histologically confirmed HER2 IHC 2 + or 3 + UC, prior received ≥ 1 standard treatment. Patients in this study received MRG002 every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST 1.1.
RESULTS: As of February 24, 2023, a total of 43 patients were enrolled. The median age was 60. 9 patients were dosed at 2.6 mg/kg and 34 patients were dosed at 2.2 mg/kg. At baseline, most patients (29/43) received ≥ 2 lines of treatment and 35 (81.4%) patients had prior ICI therapy. FISH test was performed in 41 patients and 9 (22.0%) were positive. By the cut-off date, 41 patients were evaluable and the ORR was 53% (95%CI：38.9%-67.5%), with 6.9% CR, and the DCR was 83.7% (95%CI：70.0%-91.9%). The median PFS and OS for the 43 patients were 7.0 months (95%CI：5.4-NE) and 14.9 months (95%CI：11.9-NE), respectively. The ORR was 77.8% in 9 patients with positive HER2 FISH results. Most common treatment-related AEs were anemia (51.2%), alopecia (44.2%) and neutropenia (39.5%); most were grade 1 or 2.
CONCLUSIONS: Preliminary results of MRG002 demonstrated a clinically meaningful response in pretreated HER-2 positive unresectable locally advanced or metastatic UC patients. MRG002 at 2.2 mg/kg was well tolerated with a manageable toxicity.
摘要：
背景：MRG002是一种新型的HER2靶向抗体-药物偶联物，正在MRG002-006试验中进行研究，以评估HER2阳性尿路上皮癌患者的疗效和安全性。
方法：这是一个开放标签，单臂,多中心II期研究。合格标准包括：组织学证实的HER2IHC2+或3+UC，以前接受≥1标准治疗。该研究中的患者每3周接受MRG002,直至疾病进展或不可接受的毒性。主要终点为根据RECIST1.1确认的ORR。
结果：截至2023年2月24日，共纳入43例患者。中位年龄为60岁。9名患者以2.6mg/kg给药,34名患者以2.2mg/kg给药。在基线,大多数患者(29/43)接受≥2行治疗,35例(81.4%)患者曾接受过ICI治疗.41例患者进行FISH检测，9例（22.0%）阳性。截止日期,41例患者可评价，ORR为53%（95CI：38.9%-67.5%），6.9%的CR，DCR为83.7%(95CI：70.0%～91.9%)。43例患者的中位PFS和OS分别为7.0个月(95CI：5.4-NE)和14.9个月(95CI：11.9-NE)。分别。9例HER2FISH结果阳性患者的ORR为77.8%。最常见的治疗相关不良事件为贫血（51.2%），脱发（44.2%）和中性粒细胞减少（39.5%）；大多数为1级或2级。
结论：MRG002的初步结果显示，在接受预处理的HER-2阳性、不可切除的局部晚期或转移性UC患者中，有临床意义的反应。MRG002在2.2mg/kg时耐受性良好，毒性可控。
方法：这是一个开放标签，单臂,多中心II期研究。合格标准包括：组织学证实的HER2IHC2+或3+UC，以前接受≥1标准治疗。该研究中的患者每3周接受MRG002,直至疾病进展或不可接受的毒性。主要终点为根据RECIST1.1确认的ORR。
结果：截至2023年2月24日，共纳入43例患者。中位年龄为60岁。9名患者以2.6mg/kg给药,34名患者以2.2mg/kg给药。在基线,大多数患者(29/43)接受≥2行治疗,35例(81.4%)患者曾接受过ICI治疗.41例患者进行FISH检测，9例（22.0%）阳性。截止日期,41例患者可评价，ORR为53%（95CI：38.9%-67.5%），6.9%的CR，DCR为83.7%(95CI：70.0%～91.9%)。43例患者的中位PFS和OS分别为7.0个月(95CI：5.4-NE)和14.9个月(95CI：11.9-NE)。分别。9例HER2FISH结果阳性患者的ORR为77.8%。最常见的治疗相关不良事件为贫血（51.2%），脱发（44.2%）和中性粒细胞减少（39.5%）；大多数为1级或2级。
结论：MRG002的初步结果显示，在接受预处理的HER-2阳性、不可切除的局部晚期或转移性UC患者中，有临床意义的反应。MRG002在2.2mg/kg时耐受性良好，毒性可控。
